Cytochlor Technology is about to enter a Phase I trial as a radiosensitizer of tumors of the oral cavity and oropharynx with NCI supervision. Our objective is to demonstrate Cytochlor's safety, selectivity and possible efficacy (although efficacy is not the goal of a Phase I trial). Our goal is to move Cytochlor Technology to a mutliinstitutional Phase II clinical trial, clinical practice and commercialization. We hypothesize that the elevation of dC kinase and dCMP deaminase in tumors can be exploited for a therapeutic advantage to obtain selective radiosensitization of human tumors with Cytochlor (5-chlorodeoxycytidine) and Tetrahydrouridine. We have been given a starting dose (60 mg/m2/day) based on toxicity studies in primates receiving 5-Chlorodeoxycytidine (CldC) and Tetrahydrouridine (H4U) 5 days a week for 3 weeks in which no clinical signs of toxicity were observed. H4U will be utilized at a fixed dose of 1500mg/m2/day. Patients will be entered into the trial if levels of deoxycytidine kinase and dCMP deaminase in tumors exceeds (>2.5) the levels in adjacent normal tissue. Laboratory studies will be conducted that are associated with the clinical trial including pharmacokinetic studies and metabolic monitoring of patient serum and urine with respect to levels of CldC, 5-chlorodeoxyuridine, and 5-chlorouracil. As clinical endpoints are carefully evaluated, the % of cells incorporating 5-chlorouracil (ClUra) derived from CldC and the replacement of thymiine by CdlUra in tumor and normal tissue DNA will be determined to monitor the tumor selectivity, which is the hallmark of this enzyme-driven technology as dose escalation proceeds in the Phase I trial. We will also determine the relative effectiveness with which H4U inhibits the cytidine deaminase of tumor and normal tissue. We will determine whether the enzyme profile of glioblastoma and tumors of the prostate, rectum, breast, and uterus have the ideal enzyme profile as shown for H/N tumors (elevations of deoxycytidine kinase and dCMP deaminase) as a first step in demonstrating the universal or broader application of Cytochlor Technology.